Awareness of Bacterial Resistance to Antibiotics among Healthcare Providers in Sana’a City, Yemen

Objectives: To assess the awareness of healthcare providers in Sana’a city of the most frequently antibiotic-resistant bacterial isolates encountered in clinical settings, the factors associated with the emergence of such resistance and the strategies to counteract antibiotic resistance. Methods: This cross-sectional study included 416 healthcare providers; namely, 167 physicians, 61 pharmacists and 188 nurses, from four public and two private hospitals in Sana’a. Data about demographics, awareness of the most frequently isolated antibiotic-resistant bacteria in clinical settings, the factors possibly associated with such resistance and the best strategies to counteract antibiotic resistance were collected using a pre-designed questionnaire. Data were then analyzed using suitable statistical tests. Results: The majority of healthcare providers were aware of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa as the two most frequently encountered bacterial species in clinical practice, with non-statistically significant differences in the awareness level among physicians, pharmacists and nurses. However, a statistically significant difference was found among healthcare providers regarding their awareness of the most possible factors contributing to antibiotic resistance. In this regard, pharmacists were significantly more aware of the contribution of the extensive use of newer generations of antibiotics (P = 0.030), inappropriate prescribing of antibiotics (P = 0.010) and use of antibiotics without prescription (P = 0.045) to the emergence and spread of antibiotic resistance than physicians and nurses. On the other hand, physicians and nurses were significantly more aware of the role of reducing the length of hospital stay (P = 0.005), limiting the use of medical instrumentation (P = 0.036), use of narrow-spectrum antibiotics (P = 0.005), surveillance for antibiotic resistance (P = 0.004), development of infection control policies and procedures (P <0.001) and consultation with infectious disease specialists (P = 0.010) as key strategies to minimize the emergence of antibiotic-resistant bacteria compared to pharmacists. Moreover, nurses showed significantly higher awareness of the use of narrow-spectrum antibiotics (P = 0.005) and surveillance of antibiotic resistance (P = 0.003) as key strategies to reduce the emergence and spread of antibiotic resistance. Conclusions: There is a discrepancy in the awareness of Yemeni healthcare providers’ of the most frequently encountered antibiotic-resistant bacteria in clinical practice, the factors possibly contributing to such resistance and the key strategies to counteract it. Therefore, continuing medical education of physicians, pharmacists and nurses is recommended to keep them updated on antibiotic resistance and the best strategies and approaches to its containment. In addition, there is a need for the development of infectious disease protocols for hospitals to optimize the selection and treatment with antibiotics, to reduce side effects and costs and to minimize the development of antibiotic resistance.


Introduction
Antibiotics are one of the most commonly prescribed medications worldwide, and the majority of such medications are mainly prescribed outside the hospital setting in community pharmacies (1,2). Treatment of infectious diseases caused by resistant microorganisms contributes to a considerable increase in treatment costs, disease spread, illness duration and mortality rate (3). Therefore, the emergence of bacterial strains resistant to antibiotics represents a major public health problem (4).
Multidrug resistance (MDR) in bacteria refers to their resistance to three or more agents from different categories of antibiotics, mainly antipseudomonal penicillin, aminoglycosides, cephalosporins, carbapenems, and quinolones (5,6). MDR bacteria of special concern to healthcare facilities include methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus(VRE), extended-spectrum betalactamase (ESBL)-producing Gram-negative bacteria, Pseudomonas aeruginosa and Acinetobacter baumannii (7). Several risk factors have been linked to the emergence and spread of MDR bacteria. These include prolonged hospitalization, invasive procedures, exposure to broadspectrum antibiotics, non-adherence to infection control guidelines, inadequate surveillance system and unhygienic conditions (8)(9)(10)(11)(12). In addition, irrational use of antimicrobials is one of the major drivers for antibiotic resistance, especially in developing countries (13). In Yemen, easy over-the-counter obtaining of antibiotics from pharmacies (14,15) and physicians nonadherence to rational prescribing of antibiotics (16,17) are among the factors that contribute to the emergence of resistant bacteria. Therefore, the present study aimed to assess healthcare providers' awareness of the most frequently encountered antibiotic-resistant bacteria, the factors contributing to such resistance and the key strategies to counteract it in Sana'a city.

Study design, setting and sample size calculation
This was a cross-sectional study among physicians, pharmacists and nurses working in public and private hospitals of Sana'a city during April 2016. Healthcare providers were recruited from four public hospitals; namely, Al-Thawra Modern General Hospital (TMGH), Al-Jomhori Teaching Hospital (GTH), Kuwait University Hospital (KUH) and Al-Sabeen Maternal Hospital (SMH) and two private hospitals, University of Science and Technology Hospital and Saudi German Hospital. A sample size of 383 was calculated using OpenEpi (http://www.openepi.com/SampleSize/SSPropo r.htm) after applying the default parameters and their values such as population size, anticipated % frequency, confidence limit and design effect were used. A number of 167 questionnaires were added to overcome non-respondents healthcare providers and to give a better chance to collect the required sample size.

Data collection
Data was collected using a pre-designed questionnaire composed of four sections (18). Modifications were made by the authors and then distributed to five PhD holders from the Faculty of Pharmacy, Al-Nasser University and University of Science and Technology as part of validation. All comments were considered before starting the study. Questionnaires were administered and collected through hospital visits, where participants were approached at their offices or rest areas and asked to complete the four questionnaire sections. The first section included questions about the respondent's demographic data including gender, age, occupation, level of education and specialty. In the second section, the participants were asked to answer questions regarding the most likely encountered antibiotic-resistant bacterial species. The participants had to rate six different bacterial strains known to have the ability to develop resistance to antibiotics including MRSA, VRE-faecium, VRE-faecalis, ESBLproducing Gram-negative bacteria, P. aeruginosa and A. baumannii. In the third and fourth sections, the respondents were asked to rate 12 factors that contribute to the emergence of bacterial resistance to antibiotics and 12 strategies that may reduce the development of such resistance. A four-level scale was used to rate responses as follows: 1, very unlikely; 2, somewhat unlikely; 3, somewhat likely; 4, very likely.

Statistical analysis
Data were analyzed using IBM SPSS Statistics version 21.0 for Windows ® (IBM Corp., Armonk, NY, USA). One-way analysis of variance (ANOVA) followed by Bonferroni post-hoc test was used to compare between the mean scores of independents groups for normally distributed data. On the other hand, non-normally distributed data were analyzed using Kruskal-Wallis test.

Characteristics of participating healthcare providers
Out of 550 healthcare providers invited to participate, 518 (94%) responded to the study. However, only 416 questionnaires were filled properly and subsequently used in the study.

Healthcare providers' awareness of the most frequent antibiotic-resistant bacterial strains and the factors possibly associated with antibiotic resistance
There were no statistically significant differences among physicians, pharmacists and nurses regarding their awareness of the most frequently encountered antibiotic-resistant bacteria in clinical practice (Table 2). However, there were statistically significant differences among physicians, pharmacists and nurses with respect to their awareness of the probable contribution of the extensive use of newer generations of antibiotics (P = 0.036), inappropriate prescribing of antibiotics (P = 0.020), use of antibiotic without prescription (P = 0.015) and economic and political factors (P = 0.043) to the development of antibiotic resistance ( Table 3). The Bonferroni post-hoc test revealed that pharmacists were significantly more aware of the contribution of the extensive use of newer generations of antibiotics (P = 0.030), inappropriate prescribing of antibiotics (P = 0.010) and the use of antibiotics without prescription (P = 0.045) to antibiotic resistance than physicians and nurses. On the other hand, physicians showed statistically higher awareness of the probable contribution of using antibiotics without prescription (P = 0.009) and economic and political factors (P = 0.040) to the development of antibiotic resistance compared to nurses and pharmacists.

Healthcare providers' awareness of the strategies to counteract antibiotic resistance
Regarding the appropriate strategies to limit the development of antibiotic resistance, Table (4) shows statistically significant differences among physicians, pharmacists and nurses with respect to their awareness of the utility of the following strategies to counteract the emergence of antibiotic resistance: reducing the length of hospital stay (P = 0.005), limiting the use of medical instrumentation (P = 0.036), use of narrowspectrum antibiotics (P = 0.005), surveillance for antibiotic resistance (P = 0.004), development of infection control policies and procedures (P <0.001) and consultation with infectious disease specialists (P = 0.010). Bonferroni post-hoc test revealed that physicians had significantly higher awareness of the following strategies to reduce the risk of the emergence of antibiotic-resistant bacterial strains: reducing the length of hospital stay (P = 0.005), development of infection control policies and procedures (P = 0.001) and consultation with infectious disease specialists (P = 0.032). On the other hand, nurses were significantly more knowledgeable than pharmacists re-garding the following strategies: reducing the length of hospital stay (P = 0.007) and development of infection control policies and procedures. Moreover, nurses showed significantly higher awareness of the use of narrow-spectrum antibiotics (P = 0.005) and surveillance of antibiotic resistance (P = 0.003) as key strategies to reduce the emergence and spread of antibiotic resistance.

Discussion
The awareness of the majority of healthcare providers in the present study about MRSA and P. aeruginosa as being the most frequently isolated antibiotic-resistant bacteria in clinical settings is consistent with previous findings that both species are the most frequently isolated bacteria among Yemen patients with otitis media (19,20). It is worth mentioning that the European Antimicrobial Resistance Surveillance Network specifies these two species among the seven resistant microorganisms commonly reported in several European countries (21). In addition, a recent study among Iraqi pharmacists revealed that MRSA was the most frequently isolated resistant bacterial strain (22).
In Yemen, the pattern of antibiotic prescription in the ambulatory care of public hospitals was high compared to the incidence of infectious diseases, where up to 51% of all prescriptions include antibiotics 16). Moreover, antibiotics in Yemen can be easily obtained from pharmacies without prescription (23), and such overprescription of antibiotics is one of the major risk factors for the development of resistance. The present study revealed that healthcare providers conceived that the extensive use of antibiotics, inappropriate antibiotic prescribing and use of antibiotics without prescription are major factors contributing to the emergence of antibioticresistant bacterial strains. This result is consistent with other studies reporting that inappropriate and over-prescription of antibiotics are leading causes of bacterial resistance to antibiotics (18,(24)(25)(26)(27)(28). Similarly, a recent study in hospital and community pharmacies in Iraq showed that the use of antibiotics without prescription is a significant reason for the development of bacterial resistance to antibiotics (22). On the other hand, the awareness of Yemeni physicians of the contribution of economic and political situations to the emergence and spread of antibiotic resistance is in agreement with a study conducted in 28 European countries, which indicated that corruption and poor governance are contributors to the development of antibiotic resistance (29). Nosocomial infections continue to be a major health problem in both developed and developing countries. The significance of such infections is not only attributed to the increase in morbidity and mortality rates but also to the emergence of antimicrobial resistance, prolonged hospitalization, increased healthcare cost and reduced treatment success (30)(31)(32). In this context, the present study revealed statistically non-significant differences among various categories of healthcare providers regarding their awareness of the major role of prolonged hospitalization as a contributing factor possibly associated with the emergence of antibiotic resistance. Similarly, awareness of prolonged hospitalization as a contributor to antibiotic resistance was also reported among Ethiopian physicians, pharmacists and nurses (27).  Variations in responses of various categories and specialties of healthcare providers regarding the factors possibly contributing to the emergence of antibiotic resistance in the present study might be attributed to different educational backgrounds and practice settings. Pharmacists, for example, reported that using antibiotics without prescription, inappropriate prescribing of antibiotics and extensive use of newer generations of antibiotics are the most likely factors contributing to the emergence of resistant bacteria. In the present study, physicians reported that using antibiotics without prescription in addition to economic and political factors are the factors contributing to antibiotic resistance. On the other hand, physicians and nurses indicated that prolonged hospitalization is the leading cause of antibiotic resistance, reflecting their close contact during clinical practice (order and implementation relationship). Physicians also reported that using antibiotics without prescription contributes to such resistance, highlighting the importance of taking a medication after obtaining the right diagnosis and legal drug prescription from a physician.
Identifying the factors responsible for the emergence of bacterial resistance to antibiotics is critical to the adoption of effective strategies to minimize or slow down the emergence of such resistance. Since nosocomial infections are associated with high mortality rates, poor clinical outcomes and development of antibiotic resistance, hospitals should take serious actions to minimize the emergence of antibiotic resistance. In this context, healthcare providers in the present study suggested that the implementation of appropriate infection control practice, encouragement of bacterial isolation in culture and susceptibility testing, better adherence to treatment guidelines, reducing the length of hospital stays, surveillance for antibiotic resistance and consultations with infectious disease specialists as the most likely strategies to control the emergence of nosocomial antibiotic resistance. In line with these findings, it is well documented that appropriate use of antimicrobials, reinforcement of basic infection control measures, improved hand hygiene, surveillance for antibiotic resistance and consultation with infectious disease specialists are key strategies for counteracting antimicrobial resistance (28,31,(33)(34)(35)(36)(37)(38)(39)(40)(41)(42).
The differences in the levels of healthcare providers' awareness according to their specialties in the present study could be generally attributed to the differences in their educational backgrounds and the working environments. In this regard, physicians and nurses were significantly more aware than pharmacists of the role of reducing the lengths of hospital stay, practice of infection control policies and procedures and consultation with infectious disease specialists as key strategies to minimize the development of antimicrobial resistance. This finding is consistent with those reported in other studies, which revealed a number of discrepancies in the awareness level between healthcare providers with respect to the most isolated resistant bacteria, factors that contribute to such resistance and the strategies that can be used to counteract such resistance (18,27).

Conclusions
Healthcare providers in Yemen show a discrepancy in their awareness of the most frequently encountered antibiotic-resistant bacteria in clinical practice. In addition, their awareness is variable regarding the factors possibly contributing to the emergence and spread of bacterial resistance to antibiotics as well as the key strategies that can help to counteract such resistance. Therefore, continuing medical education of physicians, pharmacists and nurses is recommended to keep them updated on antibiotic resistance and the best strategies and approaches to its containment. In addition, there is a need for the development of infectious disease protocols for hospitals to optimize the selection and treatment with antibiotics, reduce side effects and cost and minimize the development of bacterial resistance to antibiotics.